The current emphasis of this project is the mechanism of action of damage to the nervous system of organic lead compounds. The effect of organic lead compounds upon the membranes of the nervous system is being studied: 1. Membrane components that are being investigated consist of relatively widespread parameters including Na+K+ATPase, and peroxidative activity within membranes. Membrane fluidity will be studied using fluorescent probes. Regions of treated animals that are emphasized include frontal cortex and hippocampus where morphological damage is most apparent following exposure to lead. 2. Metabolic studies will reveal abnormalities of regional blood flow, glucose consumption, the ability to concentrate amino acids, and the integrity of the blood brain barrier. 3. The disruption of the normal role of calcium and zinc by lead may in part account for the effects of this toxicant on membrane structure, energy generation, and neurotransmission. Thus several enzymes and transport processs involving these essential metals are being assayed. These include phosphodiesterase, superoxide dismutase, glutamate dehydrogenase, and the synaptosomal uptake of calcium.